The term delusional infestation describes patients who present with a fixed false belief that their skin is infested with inanimate or animate objects, most commonly parasites. Delusional infestation encompasses delusions of parasitosis as well as inanimate infestations with materials such as fibers or specks, sometimes referred to as Morgellons disease. A delusional patient may be difficult to treat and may trigger a strong emotional response by the dermatologist including frustration and even anger. However, the diagnosis of delusional infestation is one of exclusion and a thorough evaluation should be performed before diagnosing this condition. This article reviews possible underlying conditions to consider in these patients, suggests an approach to the evaluation of patients, and stresses the importance of the interpersonal and psychologic aspects of the patient encounter.